Roche Holding AG (ROG) Earnings Call Transcript & Summary

My name is Henrik, and I'm the technical operator for today's call. Kindly note that the webinar is being recorded. [Operator Instructions] One last remark, if you want to follow the presented slides on your end as well, please feel free to go to roche.com/investors to download the presentation. At this time, it's my pleasure to introduce you to Bruno Eschli, Head of Investor Relations. Bruno, the stage is yours.

Thanks, Henrik. And could I have the first slide, please? So welcome to our fifth IR call this year, focusing on the latest clinical results from our malignant and non-malignant hematology portfolio, and the data, which got more recently presented at various conferences, ASCO, ICML, EHA and ISTH. Let me quickly take you through today's agenda. The event is scheduled for 75 minutes. We will have probably around 50 minutes for the presentations and then 25 minutes for Q&A. And following my quick introduction, the first presentation today will be held by Charles Fuchs, our Senior Vice President and Global Head of Oncology and Hematology Product Development. Charlie will provide a quick hematology franchise update before taking us through the latest NHL data, especially the Phase III SUNMO results for Lunsumio plus Polivy in second-line DLBCL presented last Friday at ICML, and then the 2-year follow-up data for the Phase III STARGLO study of Columvi plus GemOx in second-line DLBCL presented previously at ASCO. And finally, the Phase III POLARGO data for Polivy plus R-GemOx in relapsed/refractory DLBCL, which got presented both at EHA and ICML. Our second speaker for today will be Daud Chaudry, our Lifecycle Leader for Hemophilia Bispecifics, responsible also for global product, the global product strategy. Daud will provide us a quick update on the nonmalignant hematology franchise before taking us for the first clinical Phase I, Phase II results for NXT007, our optimized second-generation Hemlibra, which as you know, just entered late-stage development in hemophilia A. These data, he will take us through, were presented just today at ISTH. In addition to our two speakers, we will be joined for the Q&A by four additional senior franchise managers. We will have with us today, Bill Waas, our Lifecycle Leader for the NHL Bispecific Program, Global Product Strategy; Michelle Boyer, our Global Head of Lymphoma and CLL Clinical Development; Tom Van Stavern, our Lifecycle Leader for the Cell Therapy Program, Global Product Strategy; and John Pasi, our Global Head of Nonmalignant Hematology Clinical Development. Can I have the next slide, please. This slide just summarizes our current on-market hematology portfolio, which is growing strongly, as you can see, with plus 14%, delivering CHF 2.1 billion in sales just in Q1. And as you can see here, growth remains driven by all key products. Hemlibra shows a continued strong growth momentum across all patient segments and in all geographies, gaining further market shares. For full year '25, we can confirm the outlook of at least mid-single-digit global sales growth, including a strong momentum which we see in the U.S. And Polivy, a second-line DLBCL, reached another milestone with now more than 50,000 patients being treated globally and the U.S. first-line patient share exceeding 30%. Thus, we can confirm that the peak sales potential of around CHF 2 billion in first line. And of course, there are additional development opportunities such as chemo-free Ploivy, Lunsumio -- chemo-free Ploivy plus Lunsumio combination in second-line DLBCL. That's the SUNMO study, which we'll discuss today in more detail. And Polivy-R-CHP, Columvi combination in first-line DLBCL, that's the SKYGLO study, which started enrolling in 2023. Next on the list are our bispecifics. The first one here, Columvi has been launched in third line plus DLBCL globally. In the U.S., we have now achieved a share of 25%. And in second line DLBCL Columvi is launched in Europe based on the STARGLO data. Following the negative ODAC vote, second-line approval in the U.S. is pending with the PDUFA date set for July 20, Charlie will provide you here the latest update. And for our second bispecific, Lunsumio. Lunsumio is currently launching globally and third line plus follicular lymphoma with now more than 2,400 patients commercially treated and with additional development opportunities, just as for example, the Phase III CELESTIMO readout in second-line follicular lymphoma, which is expected for later this year. In addition, the Phase III SUNMO data offering a chemo-free combination of Lunsumio plus Polivy in second-line DLBCL will be filed with regulators. And to sum up, the peak sales potential for both bispecifics, overall, we have been describing the third line combined NHL-FL peak sales opportunity for both bispecifics together to be in the range of several hundred million whereas the second-line DLBCL opportunity for both together is about CHF 1 billion. And as you know, we have here two shots on goal with STARGLO and SUNMO. And then, of course, there's the first-line DLBCL opportunity based on the SKYGLO study, which then, of course, is even significantly larger. If I go down the list, the next one here is PiaSky, where the story is really about label extension in aHUS and sickle cell disease with the aHUS study reading out later in 2025. And finally, just to complete the picture, Venclexta on the bottom, where we have the collaboration with AbbVie, and which is having a leading position in CLL and first-line AML. Can we please move to the next slide. On this slide, just let me quickly summarize what has changed since the Q1 call. We provided recently a safety update for our gene therapy Elevidys in DMD following a second tragic death of a young man in the non-ambulatory setting due to fetal acute liver failure. The benefit risk profile was reassessed and found to be unfavorable for patients with DMD who are non-ambulatory. This basically cuts the number of patients, which could be reached, in half, which is reflected here in the updated numbers. And with regards to the Phase III dose, besides moving trontinemab in Alzheimer's disease and NXT007 in hemophilia A into Phase III, we have taken two additional decisions in Q2. One is zosurabalpin, our first-in-class novel antibiotic. And then as announced in a top line release, the second one, prasinezumab in Parkinson's disease. And let me just quickly comment here on the prasinezumab position. This decision was also based on the 6-month open-label extension data for the PDUFA study, which we have now in-house and which indicates that the benefit gets more pronounced over time. similarly to what we have seen previously in the initial PDUFA open-label extension. Also, keep in mind, the future Phase III study will take all these Phase II learnings into account, including choosing the optimal patient population, patients on levodopa had a more pronounced benefit, the right endpoints or appropriate -- the appropriate length of these studies. Can I have the next slide, please. To complete the picture, this is the updated key news flow slide. So currently, all studies are on track as previously communicated. Compared to the Q1 call, we had a negative readout for Venclexta in first-line MDS, which has been communicated by our partner, AbbVie. And what you also can see here, we still have two more studies in hematology to read out in 2025 that is the Phase III CELESTIMO study for Lunsumio plus lenalidomide in second light plus follicular lymphoma towards year-end and then the Phase III COMMUTE-a study for PiaSky in aHUS. Next slide, please. And finally, for the upcoming events, following the half year results on July 24, we will hold again our annual Pharma Day in London on September 22, providing again an extensive update of what has happened throughout the last year. And with that, I will close and let me hand over to Charlie for the hematology franchise update. Charlie, please.

Thank you, Bruno, and thank you, Bruno, and thank you for the opportunity to share some key highlights of our hematology portfolio presented at ASCO and the recent and even ongoing heme summer congresses. As you all know, Roche and Genentech have a rich legacy in transforming the therapeutic landscape in cancer and blood disorders. We're leveraging our broad portfolio of molecules to advance best-in-class precision medicines such as the inavolisib, our best-in-class PI3K inhibitor in divarasib, our best-in-class KRAS G12C inhibitor. We're focused on novel modalities, including our next-generation off-the-shelf allogeneic CAR-T therapy in collaboration with Poseida Therapeutics and our next-generation ADCs, such as our cMET ADC. We're also committed to rational and high-impact combination regimens such as Lunsumio-Polivy, which I'll talk about in a moment in the SUNMO trial. And obviously, our growing portfolio in hormone receptor positive breast cancer. Finally, and no less importantly, Roche is committed to improving on the standard of care, including treatment standards that we ourselves have set, specifically in hormone receptor positive breast cancer, we seek to set a new standard backbone of endocrine treatment with our best-in-class selective endocrine receptor degrader giredestrant. And in hematology, we've transformed millions of lives with Hemlibra, and we're now working on our next-generation bispecific, NXT007, which Daud will talk about in more detail shortly. Turning to the next slide. We're privileged to develop one of the broadest and richest portfolios of novel molecules in hematology, targeting a series of both malignant and non-malignant hematology conditions at various stages of development, including assets under registration review with health authorities or commercially available molecules advancing the lives of patients with hematologic disorders. I won't be able to cover all of these agents in our portfolio, but I'll highlight a few programs as will Daud, and we obviously will be available for your questions during the Q&A. Turning to the next slide. Further building on that portfolio is our entry into cell therapy with our acquisition of Poseida Therapeutics. CAR-Ts have transformed the landscape of hematologic malignancies, but they're highly complex and ultimately, only about 25% of patients eligible for CAR-T actually receive CAR-T because of the need for apheresis, processing delays, bridging therapy. Our approach developed with Poseida leverages their healthy donor-derived stem cell memory T cells. These cells are long-lived, self-renewing and capable of differentiating into the entire spectrum of T cell subsets to lead the effective response against cancer, enabling durable antitumor protection as well. We leverage Poseida's nonviral gene editing technology, allowing stable integration of multiple CARs as well as high-fidelity knock-in and knockouts to enhance efficacy and reduce adverse events. We believe this off-the-shelf, immediately available CAR-T approach will allow us to truly democratize cellular therapy. Our lead program is a BCMA-ALLO CAR-T currently in Phase I in relapsed/refractory multiple myeloma, demonstrating, as you can see on the right, high response rates in heavily pretreated patients and was granted RMAT designation by the FDA. Beyond that, we have a CD19, CD20 dual CAR program currently in Phase I trials in B-cell malignancies and we've been recently granted additional FDA INDs for multiple sclerosis and systemic lupus erythematosus. Turning to the next slide. I'd like to turn our attention now to our recent data in non-Hodgkin lymphoma presented at ASCO, EHA and ICML. Non-Hodgkin lymphoma accounts for nearly half of all hematologic malignancies with diffuse large B-cell lymphoma, the most common form of aggressive NHL, and follicular, the most common of indolent. More than 25 years ago, our CD20 targeting monoclonal antibody, Rituxan, transformed the landscape and remains a mainstay for the treatment of B-cell malignancies. Subsequently Gazyva, a humanized, engineered monoclonal inducing greater ADC and direct cell death represents an important part of the treatment in CLL in follicular lymphoma. Our first-in-class ADC, Polivy, a targeting CD19, 79B, was initially approved in relapsed/refractory DLBCL. And as you know, is now an integral part of the first-line curative therapy for large cell lymphoma. Today, our CD20, CD3 bispecifics, Columvi and Lunsumio, are leading the next generation of therapies with approvals in the third-line settings of DLBCL and follicular, respectively. Turning to the next slide. As shown in the slide, we have a comprehensive program of clinical trials across the range of NHL and subtypes and other hematologic malignancies. The list on the left is not exhaustive but is a strong representation of the breadth of our clinical program. Polivy has had a strong uptake in first-line DLBCL, which, as Bruno pointed out, over 50,000 patients treated. Today, I'll be sharing new data, including the results of the POLARGO of Polivy, R-GemOx in relapsed/refractory DLBCL as well as 5-year uptake for the POLARIX study in the first-line setting. We launched Lunsumio monotherapy in over 60 countries, now with over 3,000 patients treated in the third-line setting of follicular lymphoma, and I'll share today data for the subcutaneous formulation of Lunsumio filed with health authorities as well as data of novel combinations that is Lunsumio in combination with Polivy, among others, in our positive SUNMO trial. Columvi monotherapy is now approved in over 60 countries in the third-line setting of diffuse large B-cell lymphoma with over 6,000 patients treated, including over 2,000 in the U.S. At this week's ICML, we provided an update of the STARGLO study, which is now approved in over 30 countries, including the EU. Turning now to the next slide. Building on the convenient outpatient administration of Lunsumio, we reported data for our subcutaneous formulation of Lunsumio, showing non-inferiority exposure as compared to IV administration with, as you can see, similar progression-free survivals. The subcu formulation advances patient convenience for this fixed duration off-the-shelf outpatient therapy and provides important efficiency and cost savings as compared to such alternatives as CAR-T therapy. Lunsumio subcutaneous has been submitted for approval with both the U.S. FDA and the EU in third-line follicular lymphoma. We're also investigating subcu Lunsumio as a monotherapy in previously untreated patients with high tumor burden follicular lymphoma in our Phase II MorningSun trial shown on the right, showing a compelling 87% response rate and a 61% complete response rate in conjunction with a very manageable safety profile. In this trial, we observed a low rate of cytokine release syndrome, which was principally low grade, reflective of the convenience and ease of administration for subcu formulation. MorningSun is being conducted largely at community sites, given the appeal of therapy to community oncology centers. Turning to this slide, you see before you. At the same time, we're studying the combination of subcu Lunsumio with lenolidomide in first-line high tumor burden follicular lymphoma. At ICML, we presented longer follow-up on the combination of Lunsumio and lenolidomide using the subcu formulation of Lunsumio, showing that this chemo-free outpatient regimen provides highly durable, robust responses with a response rate of 90% and a complete response of 88%. With respect to durability, 12-month event progression-free survival is 87% and 12-month event-free overall survival is 97%. Moreover, this represents -- this regimen provides a very manageable safety profile. Again, low rates of CRS that are largely low grade. Next slide. We're also partnering with cooperative groups, LYSARC and GLA to investigate the combination of Lunsumio-len as a potential new standard of care in the first-line setting of follicular lymphoma. The MorningLyte study started recruiting last year and enrolled almost 800 patients, comparing Lunsumio-lenolidomide to R or G-chemo in the first-line setting. In the second-line setting on the right of follicular lymphoma, we're conducting the CELESTIMO study comparing Lunsumio-lenolidomide to Rituxan-len, and we expect to report out results from CELESTIMO at the end of this year. Turning now, we're also advancing other combinations with our bispecifics, and at the ICML meeting, we shared positive data from our SUNMO study of Lunsumio and Polivy in the second-line plus setting of diffuse large B-cell lymphoma. Let me recap some of these data for you now. So turning to the first slide. SUNMO enrolled patients with transplant ineligible second-line plus DLBCL, which also included patients with high-grade B-cell lymphoma double hits, transformed follicular lymphoma and Grade 3b follicular lymphoma, so a broad population. Patients were randomized to receive either the combination of Lunsumio and Polivy or R-GemOx with the primary endpoint of progression-free survival. Turning to the next slide, as reported this week, patients randomized to Lunsumio-Polivy experienced a 59% reduction in the risk of disease progression or death when compared to R-GemOx with a median progression-free survival of 11.5 months for Lunsumio-Polivy and 3.8 months for R-GemOx. Turning next, this translated into a 12-month progression-free survival of 49% from Lunsumio-Polivy as compared to 18% for R-GemOx. Turning now to response. The combination -- on the next slide. The combination of Lunsumio-Polivy also conferred a robust and statistically significant improvement in objective response with a 30% absolute improvement in overall response rate, 70% versus 40%, and a doubling of the complete response rate, 51% versus 24%. Turning next on the slide to safety, the chemo-free regimen of Lunsumio and Polivy, was delivered entirely as an outpatient and associated with a very manageable safety profile, with AE rates comparable to R-GemOx. In fact, there were fewer adverse events leading to treatment discontinuation in the Lunsumio and Polivy arm. Lunsumio-Polivy was also associated with low rates of cytokine release syndrome, which were principally low grade. Turning now to the conclusions, SUNMO is the first Phase III study of essentially a chemo-free regimen in diffuse large B-cell lymphoma. As compared to R-GemOx, Lunsumio-Polivy reduced the risk of progression or death by 59%, tripled the median progression-free survival and doubled the complete response rate. Moreover Lunsumio-Polivy has the high -- has rather the lowest, forgive me, the lowest cytokine release syndrome incidents and severity among T cell directed therapies to date. Ultimately, this fixed duration chemo-free outpatient regimen provides a clinically meaningful and statistically significant improvement in progression-free survival and the overall response rate in patients with transplant ineligible, relapsed/refractory diffuse large B-cell lymphoma, and we think represents an important new opportunity as a standard of care. Turning to the next slide. Turning now to our other CD20, CD3 bispecific, Columvi, we provided an important update to the STARGLO trial of Columvi and GemOx in transplant ineligible second-line plus relapsed diffuse large B-cell lymphoma. Turning to the next slide. As a reminder, STARGLO randomized patients to either Columvi, GemOx or R-GemOx with the primary endpoint of overall survival, delivering a 41% improvement in overall survival, a 63% improvement in progression-free survival and a statistically significant improvement in complete response rate going from 25% to 59% with Columvi-GemOx. Adverse events were consistent with the known safety profiles of the individual agents and no new safety signals were noted. We submitted these impressive data to health authorities around the world leading to approvals now in over 30 countries to date, including the European Union. Also, on the basis of the STARGLO results, a panel of U.S. lymphoma experts selected Columvi-GemOx as a category 1 treatment recommendation for the NCCN guidelines in the U.S. We also submitted the data to the FDA last year, which, as you know, was brought to an ODAC last month regarding the applicability of the data to U.S. patients. Turning to the next slide. The concern raised by the U.S. FDA stems from the exploratory analyses in STARGLO pictured on the left in the forest plot. Specifically, we saw a consistent benefit for Columvi-GemOx among virtually all of the 77 subgroups studied in exploratory analyses. However, we saw variations in the overall survival hazard ratio among the subgroups of race and most notably, region of enrollment. While the ODAC committee recognized the overall benefit of STARGLO for -- in the intention-to-treat population, they wanted additional data to ensure applicability to the U.S. population and voted no on the question of applicability to the U.S. population. It should be noted, however, that STARGLO was not designed nor powered to study exploratory subgroups, and across all studies of Columvi monotherapy, there have been no regional differences in pharmacokinetics, efficacy or safety ever observer. Additionally, as shown in the right panel of this slide, within STARGLO, the effect of Columvi-GemOx on overall survival was consistent across all regions of the world, enrolling patients. Turning to the next slide. Furthermore, within the subgroup of North America, Europe and Australia, Columvi-GemOx delivered a 42% improvement in event-free survival and a consistent improvement in complete response as shown on the right-hand panel. Ultimately, STARGLO was the well-conducted Phase III trial that delivered on its primary endpoint showing a 41% reduction in the risk of death in the intent-to-treat population. Based on these ITT data, we believe that STARGLO data are applicable to U.S. patients, and we are continuing discussion with the FDA and, as Bruno noted, with a PDUFA date of July 20. Turning to the next slide. At both ASCO and this weeks' -- last week's ICML meetings, we provided important updates to -- sorry, if we could just advance the next slide. Yes, thank you. Important updates to the STARGLO trial. So now with 2-year follow-up, we continue to see a clinically meaningful improvement in overall survival for Glofit-GemOx with a 40% improvement in overall survival. I want to point out that the median overall survival for the Glofit-GemOx arm has still not been reached. Turning to the next slide. Moreover, with longer follow-up, the progression-free survival benefit for Columvi-GemOx is sustained demonstrating a 59% improvement in progression-free survival with a median progression-free survival of 13.8 months for Columvi-GemOx as compared to 3.6 months for R-GemOx. Turning to the next slide. STARGLO included patients who had progressed on one or more prior lines of therapy. As this audience is aware, a number of important treatment options have emerged in the second-line treatment of DLBCL, including most notably, CAR-T. Nonetheless, due to its complexities and limited availability, as I mentioned earlier, only 25% of patients who are eligible for autologous CAR-T actually receive CAR-T therapy. To isolate the impact of Columvi-GemOx in the second-line setting, we analyze the results of this trial among patients receiving only second-line treatment as shown in the second-line cohort, Columvi-GemOx conferred a 24-month overall survival of 60% and as compared to 39% for R-GemOx with a suggestion of a plateau of the overall survival curve in the Columvi-GemOx arm. While longer follow-up will be important, these results document the sustained and clinically meaningful benefit of Columvi-GemOx in the second-line setting of diffuse large B-cell lymphoma. Turning to the next slide, with longer follow-up in STARGLO, safety remains unchanged compared to the primary analysis and is consistently manageable with CR rates that are low and principally low grade. So turning next to the conclusions. In sum, STARGLO documents the sustained survival and response benefit for Columvi-GemOx with 2 years of follow-up. Additionally, with this fixed-duration therapy, we observed robust immune recovery 18 to 24 months after the end of therapy, even with the sustained lymphoma response observed with this therapy. We believe these data support the Glofit-GemOx -- rather Columvi-GemOx as an important fixed duration off-the-shelf therapy that meaningfully extends survival. Turning to the next slide. We're showing now both the results of STARGLO and SUNMO, and it's important to recognize that cross-trial comparisons should always be viewed cautiously. Nonetheless, I would suggest that STARGLO and SUNMO bring us one step closer to our goal of improving outcomes for as many DLBCL patients as possible. While both studies enrolled broadly similar relapsed/refractory large-cell populations, SUNMO included a slightly more heavily pretreated and higher-risk cohort. Nonetheless, each regimen offers distinct advantages that expand the treatment arsenal for physicians. STARGLO is the first bispecific-based regimen to demonstrate an overall survival benefit in this setting and represents a powerful option for patients who can tolerate chemotherapy. However, we recognize that Columvi-GemOx may not be appropriate for all patients. In contrast, SUNMO offers a chemo-free outpatient-based regimen with a milder safety profile that may be more accessible for older or more fragile patients. We should note that in contrast to STARGLO, overall survival for SUNMO remains immature and will require a longer follow-up for a mature estimate of the secondary endpoint of overall survival. In sum, the regimens in both STARGLO and SUNMO brings somewhat different therapies, but each provides very meaningful benefit to relapsed/refractory DLBCL patients and nicely complement each other. We continue our discussion with the FDA on STARGLO. Data from SUNMO will be submitted to health authorities, including the FDA. And both of these studies will continue with follow-up, and we will continue to advance new therapies for relapsed/refractory DLBCL patients. Turning to the next slide. Beyond SUNMO and STARGLO at both EHA and ICML, we presented results for the Phase III POLARGO study of Polivy-R-GemOx in second-line plus DLBCL. As compared to R-GemOx, Polivy-R-GemOx conferred a statistically significant and clinically meaningful 40% improvement in overall survival for patients in transplant ineligible relapsed/refractory DLBCL, further strengthening the body of evidence for the use of Polivy in combination with chemotherapy for DLBCL patients. This benefit was consistent across subgroups, which are not shown here, including showing a consistent benefit across cell-of-origin subclasses and had a safety profile in line with the individual components of the regimen. Ultimately, POLARGO offers additional Phase III evidence for the benefit of Polivy in DLBCL. Nonetheless, we maintained that the most important benefit for Polivy is in the curative first-line setting of DLBCL, where Polivy has been added to frontline chemo immunotherapy in the previously documented POLARIX trial. Turning to the next slide. And to that point, we -- on the next slide. We -- as you recall, POLARIX had demonstrated -- can you go back to the POLARIX side. Thank you. POLARIX demonstrated the superiority of Polivy-R-CHP over R-CHOP in the first-line setting of DLBCL. At the most recent ASH meeting, we presented updated 5-year data for Polivy-R-CHP and the PFS and CR, complete response, benefits were maintained in 5 years. Additionally, while the overall survival remains immature with longer follow-up, the hazard ratio for overall survival is trending towards a greater improvement with an overall survival at that analysis with a hazard ratio of 0.85. Importantly, patients treated with Polivy-R-CHP in first-line DLBCL, we're far less likely to require additional subsequent therapy for lymphoma, namely only 38% of patients treated with Pola-R-CHP required subsequent therapy as compared to 62% treated with R-CHOP. Longer follow-up is planned for POLARIX, and we look forward to sharing more mature overall survival results at that time. Turning to the next slide. Also, at ICML, we provided updated data for the addition of Columvi to the Pola-R-CHP regimen demonstrating an overall response rate of 100% with a complete response rate of 96%. As shown on the left panel, responses were highly durable, and the treatment was well tolerated with a relatively low rate of cytokine release syndrome. The regimen is being studied in the ongoing Phase III SKYGLO trial, comparing Columvi-Pola-R-CHP to Pola-R-CHP regimen. Of note, SKYGLO has been enrolling well, and it is the only Phase III trial in which a bispecific is being added to the Pola-R-CHP regimen, which we think has the opportunity to give patients the best chance for cure in diffuse large B-cell lymphoma. I want to thank you for the opportunity to share these exciting data, and I now want to turn to Daud to share equally exciting work in our non-malignant hematology portfolio.

Thank you, Charlie, and thank you very much for sharing that exciting update. My name is Daud Chaudry, I'm the hemophilia lifecycle leader for our bispecifics, and I'm really pleased to be able to give another exciting update on our non-malignant hematology portfolio. So if we can move forward, please to the next slide. So we have a robust and very promising pipeline in non-malignant hematology, including our long-term corporate commitment towards hemophilia A. Of course, this is based on Hemlibra, the global standard of care in hemophilia A, which we launched back in 2017, but we'll talk a little bit about our broader portfolio first and then get back to hemophilia, where we'll share both an update on Hemlibra, our future portfolio and some exciting data that came out at ISTH yesterday. First and foremost, when we look at PiaSky, our product for complement, we have a couple of important data readouts later this year in aHUS and sickle cell disease to further broaden our portfolio, including PNH with the PiaSky portfolio. Additionally, we will also be reading out further data from Hemlibra. We did earlier this year at [ EHA ] with our interim analysis on beyond ABR. We'll be reading out data and starting our Phase II on SPK-8011QQ as well as, of course, the Phase I/II data for NXT007, and as we communicated in Q1, the move forward towards Phase III for NXT. Now moving back to Hemlibra, Hemlibra has established itself as a global standard of care in hemophilia A. We continue to see patient growth, particularly in the moderate and severe patients who remain on Factor VIII who are continuing to choose Hemlibra and grow at a great rate. We have an outstanding profile with about 2/3 of the patients choosing Q 2-week or Q 4-week subcu dosing, and we continue to advance our improvements in patient experience. including new vial options, an updated administration kit and of course, an auto-injector that we have in development to make sure patients have an excellent experience in administration as well as from a therapeutic perspective. Now let's talk a little bit about why Hemlibra has become the global standard of care. We move forward to the next slide. So we have extensive real-world data. We have seen efficacy in both the real world as well as our robust clinical program. Hemlibra has the broadest clinical program in the hemophilia space, and we have demonstrated sustained bleed protection with low ABR as well as greater than 80% of patients with 0 treated bleeds in some of our real-world data. This has been established in greater than 100 real-world data publications with over 10 years of study and over 28,000 patients treated across the globe. We have an established favorable safety profile, looking at over 10,000 people in those real-world data studies as well as our clinical program, and Hemlibra does not induce Factor VIII inhibitor development. We have multiple dosing options to fit patients' lifestyle with the great majority of them choosing Q 2-week or Q 4-week subcu administration, and we continue to advance, as I mentioned, the patient administration options, leading up to and including our auto-injector. But even though Hemlibra is the current standard of care and is doing excellent things with additional patients choosing every day, we want to really continue to push ourselves as a long-term commitment to hemophilia A to continue to bring innovative therapies towards the hemophilia community. And if we move to the next slide, I'll talk through a couple of our next products in our product portfolio. SPK-8011QQ really is the next-generation gene therapy in hemophilia A. It combines an enhanced function Factor VII variant with a well-described AAV capsid and vector platform. So this pulls forward the SPK-8011 durable factor expression, favorable safety profile and low infusion reactions and couples it with 8011QQ, which is the variant, as you can see on the right side, that actually improves hemostatic potential by modifying 2 amino acids that help resist activated protein C degradation. This gives SPK-8011QQ the possibility to reach normalized levels of hemostatic potential and minimizing any need for additional Factor VIII prophylaxis or additional bleed protection. The Phase IIb is currently ongoing, and we're very excited about the potential for the next-generation gene therapy with SPK-8011QQ. Moving forward to another portfolio product that I'll focus on quite a bit today, which is NXT007. So NXT007 truly is the next-generation Factor VIII mimetic bispecific. We are building upon the Hemlibra backbone with some modifications to improve both the potency and the potential for hemostatic normalization. If you look at the middle chart, you can see Hemlibra compared to NXT in the preclinical setting, looking at peak height of thrombin generation as well as a left shift on the graph compared to emicizumab, demonstrating increased potency. NXT007 is about 30-fold more potent than Hemlibra in, in vitro assays and thrombin generation. This gives us the potential to improve bleed protection in a very convenient low dose and achieve hemostatic normalization. We are reading out the data for the Phase II, both at ISTH here, and we'll have additional Phase II data at a conference later this year. And as I mentioned before, Roche has made the decision to move forward to Phase III with 3 Phase III trials, including a head-to-head with the current standard of care, Hemlibra, early in 2026. So if we can move forward, please. What I'd love to do now is help you with some of the data that was presented by Dr. Shima yesterday at ISTH Conference. This data helped form some of their decision to move forward to Phase III, in addition with the preclinical data and the NXTAGE Part A data that was presented at ISTH last year. So if we can move forward, I'll walk through the data for the Phase I/II multiple ascending dose trial. So this is the first time we're studying NXT007 in people with hemophilia A. There were 4 different cohorts that were designed based on PK simulations to look at the effect of Hemlibra in people who had not previously been treated with Hemlibra. These are severe hemophilia A patients without Factor VIII inhibitors between the ages of 12 and 65 years old. We analyzed them for safety, tolerability, PK, pharmacodynamics and efficacy in these Hemlibra naive patients. And the primary analysis was, when greater than or equal to 6 patients completed 16 weeks of NXT007 per cohort. And the 4 cohorts, B-1 through B-4, had a loading dose phase and then a maintenance dose of the different doses you see here from 0.072 mgs per kg to 1.08 milligrams per kilogram. And their data on bleeds was compared to the previous 24 weeks of recall data on their bleeds. And if we can move forward to the next slide, please. Thank you. So looking at the PK data. If we look at the different cohorts, looking at Cohort B-2 in the green line, this cohort was made to demonstrate the threshold for non-hemophilic levels of hemostatic potential. And moving above that to B-3 and B-4, these were really in the normal range from a predictive modeling of hemostatic potential. And what we can see is nice, consistent PKs that also show a very strong dose dependency with the top 2 being solidly in the normal range of plasma concentration as well as the predicted value. So if we can move forward, PK analysis is clear. How does this translate to bleeds? So we really see the next NXT007 Phase II results as having the potential for best in disease efficacy. Looking at the previous treatment arms in gray before enrollment on the number of bleeds that were looked back upon versus the ABRs in the maintenance dose period in blue, we can see both a clear differentiation from previous treatment to -- or excuse me, NXT007 treatment across all of the different cohorts. And in fact, in the top 2 cohorts where we see the normalization potential, we had 0 treated bleeds during the maintenance period. This is extremely important, and this is very significant data from a bleed protection perspective. And if we could move forward, please, we'll talk a little bit about safety. Through all the dosing regimens, NXT007 was well tolerated across all doses. There were no dose-dependent increases in adverse events or thrombotic issues reported. All of the AEs and serious adverse events that led to discontinuation were not related to NXT007. Injection site reactions were only in 4 patients, and they were very mild. And from an ADA perspective, we only saw 2 ADAs that impacted PK in the 30 participants. One of the participants did discontinue NXT007 treatment and an additional patient stayed on and did not have any bleeds. And very importantly, there were no ADAs that cross-reacted with Hemlibra that we observed. So if we can move forward to the conclusion slide, please. So in conclusion, we really are looking at NXT007 as the next generation in hemophilia bispecifics. There is the potential, particularly looking at the B-3 and B-4 cohorts to have 0 bleeds, and those were predicted to be in the normal level from an ABR perspective, all of them decreased relative to baseline for all of the different 4 cohorts, but B-3 and B-4 really demonstrated 0 bleeds in that maintenance done. This is the ability for us to build upon the success of Hemlibra with a well-engineered molecule in NXT007, and no additional safety concerns were observed even in the highest cohort. This data, coupled with the previous data we've shared on NXT has given us the confidence to move forward into 3 Phase III trials, including a head-to-head versus Hemlibra to be initiated in early 2026. And in addition to SPK-8011QQ and our non-malignant hematology portfolio, we are very proud of our current product portfolio, leading the standard of care in hemophilia as well as the future potential of our portfolio to further elevate and transform hemophilia care. Thank you. And I'll hand it back to Bruno.

Thanks, Daud. Excellent. So we are already done with -- at 45 minutes. We'll open the Q&A session. Currently, no hand has been raised. So let's see whether someone will come with the first question. Yes. There we go. It's Colin White from UBS.

I just wanted to ask a pretty basic one about -- obviously, we saw some competitor data in the hemophilia A as well at the conference. And I just wanted -- if you could talk a little bit about how you see the market -- the hemophilia A market playing out with that competitor reaching the market, the options that you're giving with Hemlibra, the new things that you're offering with Hemlibra. So how you see it playing out? And then when we could expect NXT007 to reach the market, and what you would expect to happen at that point? And then I guess a part of this question as well is if you -- that's on the Factor VIII side. But then if you could explain a little bit about how you see the gene therapies -- your new gene therapy coming in and fitting into treatment, that would be helpful as well.

Bruno, would you like me to take that?

Yes, please.

Great. I was waiting for you. Right. Yes. So there differently was a couple of competitor data readouts here. And I think from our perspective, we have committed as a company really to looking at transformative change. We don't want to bring sort of incremental change within the hemophilia space. That's one of the reasons we're doing a head-to-head with NXT007 against Hemlibra. We believe we really need to be able to beat the standard of care, not just bring an additional option for patients. And with SPK-8011QQ, we're attempting to do the same thing with really looking at the potential to normalize hemostasis. Seeing the data that's coming up from a competitive perspective, of course, one of the biggest challenges is that there is no head-to-head data. For whatever reason, the two competitors have chosen not to go head-to-head with Hemlibra, and we understand potentially why they're choosing to do so. We don't see a ton of differentiation in the data we've seen thus far, and we want to make sure that we are also continuing to differentiate. We're creating real-world data, years of evidence, a broad clinical program and of course, the auto-injector we have in development to make sure Hemlibra is competitive today as we bring forward NXT007 and SPK-8011QQ in the future to further elevate treatment. So we still think there's opportunity, but that opportunity, we think, is really going to be enhanced through our own portfolio. Additional products are creating options for patients, but we're not seeing data that is compelling from that perspective. As far as NXT007 and when we will reach the market, a lot of that really depends, obviously, on the rate of trial recruitment. So as I mentioned, we're going to initiate our Phase III at the beginning of 2026, and we'll see how quickly we can recruit. Our goal is to bring the product to patients as soon as possible. And then lastly, from a gene therapy perspective, one of the things that's important to us from a strategic perspective as well is not just to bring transformative therapies but to bring transformative options. And so in addition to having NXT, we know there is demand from within the hemophilic community for gene therapy. And we wanted to make sure that we can offer a gene therapy option that will really advance care. And so for those who would choose gene therapy, typically, they're looking for solutions that don't involve routine prophylaxis. And of course, NXT007, we expect to be a best-in-disease prophylaxis.

Colin, did we answer all your questions?

Yes.

Okay. Next would be Steve Scala from Cowen.

And I apologize if you just answered this question, but I wasn't clear based on the answer. Is the head-to-head of NXT007 versus Hemlibra powered for noninferiority or superiority? I know you seek superiority, but is that how the trial is powered? And when are biosimilars of Hemlibra are expected?

Yes, so -- go ahead, Bruno.

Yes, maybe, Daud, I can just take the second question. In terms of the communication for the loss of exclusivity, we have so far only communicated it will be beyond 2030, which is our standard cutoff range.

And I'll answer the second one. We're still in discussions, both internally and with health authorities around the design of our Phase III program. And so it's a little premature to fully answer that, but I think you correctly mentioned, obviously, our goal is to demonstrate superiority and also make sure we can fully characterize the potential of NXT007. So stay tuned for more information on that trial design as well as the potential for readout there.

Steve, all questions from your side?

Yes.

Okay, then maybe I will quickly read one question, which came in here written and this would come from [ Aliya Parikh ] and she's asking, is Mosun-Pola expected to be administered in the outpatient setting when Pola administration has to be IV? So it's a bit about how we expect the market to segment and maybe what we can -- what we want to do in terms of further developing the administration?

Thank you, Bruno. I can take this one. And I assume it's in reference to the SUNMO regimen. So patients will still need to go to the clinic to get their treatment. However, they have the possibility of going home after they receive it. This is in contrast to other approved bispecifics in therapies like CAR-T and DLBCL, which currently require overnight hospitalization for one or more infusions. So fully outpatient administration has the advantage of being more convenient for patients and allows treatment in communities that do not or may not have a nearby or a local hospital. We think when this is coupled with a fixed duration of therapy, a very simplified administration schedule for bispecific that SUNMO will be really attractive regimen for community oncology practices, which happens to be where most patients are treated in countries like the U.S.

Thanks, very clear. Then maybe any other questions? If not, then -- David Evans -- now question has come in. David Evans from Kepler.

Sorry to be late to the question. But just -- I just wanted to check in about the -- in the Hemlibra study -- sorry, the NXT study about the occurrence of antidrug antibodies. So they did occur in most patients. I was just wondering the clinical relevance, how those will be monitored, what the kind of downside is if those do occur just because we've seen relatively little exposure so far. But I mean, would you expect those to go up over time? And how much of how much an issue could that be?

Yes. Thank you. Certainly, we saw, as I mentioned, only two that had PK impact to date. And in fact, the one did discontinue. So there was clinical manifestation within that patient and they discontinued therapy. The second person who had PK impact did not see any clinical implications, meaning they had no bleeds during the maintenance period. And in fact, they stayed on NXT007. Their rates stayed around the B-1 level, so still within the -- clearly, the protective level from a bleed protection. And I think one thing we have to do is continue to observe this. We have more Phase II data reading out later this year, and then we will certainly look in the robust and broader patient population in the Phase III to help better characterize the ADA. But though we saw a high proportion in the trial demonstrate ADA at some point, even at the end of the maintenance dose of the 22 that showed ADA, only 10 still had demonstration of ADA and only two again had PK impact. So that's the data that we have so far. I think looking forward in the future, we'll better characterize that with our additional Phase II data later this year and then certainly within the broader population in the Phase III.

Then next question comes from Justin Smith from Bernstein Societe General.

Just a quick one. I'm just trying to go back to Colin's question just to try and get a bit of a sense on the timing of the launch because the bar is so much higher here than when you launched Hemlibra, can you just talk -- can you say anything about the number of patients that would be required in a Phase III trial of 007 versus Hemlibra? Or is it too early to even talk about that?

It is still a bit early to talk about it. But as you can imagine, we're not setting ourselves a low bar. We want to be able to demonstrate the impact of NXT007. And on the other side, we are having very strong interest in the trial from a community perspective. So we'll see as we move into the Phase III, how quickly we can recruit this. But I think -- as I said, the level of interest as of right now is very high even with potential patient demands.

Maybe to add here, Daud, I think, Justin, with respect to your question, I think there's enough time between the readout of these studies and the loss of exclusivity of Hemlibra coming. So it's not very tight there. It will be -- work out. Just asking again whether there are any more questions? If not, I think then we would be at the end of our call. And I would like to thank all of our speakers here for their time and commitment in preparing. Let me also thank a couple of the IR team members, Richard [indiscernible] for the working on presentations at the overall lead for the call. And also, [ Jan Philip Schwan ] for developing slide decks and [ Melanie Wolf ] from the back office for the event organization. I hope this event was helpful providing the latest update on our heme franchise. And if you have any remaining questions, then please reach out to the IR team. We are always happy to assist. And other than that, I wish you a good weekend, and talk to you soon. Bye-bye.